Method for determining the effectiveness of a sterilization method for a medical product in a sterilizer, data processing system, computer program product, and medical product

ABSTRACT

A process is presented for determining the effectiveness of sterilization processes for medical devices, with the steps of: providing a data structure, wherein the data structure represents a grid formed of a plurality of three-dimensional cells, recreating the medical device arranged in the sterilizer in the data structure in such a way that a first plurality of cells of the grid represent a body of the medical device and that a second plurality of cells represent an interior of the sterilizer which is not occupied by the body of the medical device, recreating an initial state in the data structure in such a way that each cell of the second plurality of cells is assigned data with respect to the temperature prevailing at the location of the cell, the quantity of a first medium located in the area of the cell and the quantity of a second medium located in the area of the cell, recreating, step by step, changes in the temperature, the quantity of the first medium and the quantity of the second medium occurring in each cell of the second plurality of cells during the sterilization process, and calculating a reduction of a germ load achieved in each cell of the second plurality of cells during the sterilization process taking into account the prevailing temperature, quantity of the first medium and quantity of the second medium in the respective cell in each step. Furthermore, a data processing system as well as a computer program product for carrying out the process are presented.

The invention relates to a process for determining an effectiveness of asterilization process for a medical device or a packaged medicinalproduct in a sterilizer. For sake of brevity the following disclosuremainly refers to medical devices, while each reference to medicaldevices shall also include packaged pharmaceutical products.

Sterilization processes are used to sterilize medical devices orpackaged medicinal products prior to their use, thus to rid them ofpotentially harmful germs. Known sterilization processes comprise steamsterilization, dry heat sterilization, autoclaving, gamma sterilization,electron beam sterilization, ethylene oxide sterilization and plasmasterilization. Within the framework of this application, medical devicealso denotes medicinal products, in particular packaged medicinalproducts, further in particular medicinal products packaged in bags,further in particular solutions and devices for peritoneal dialysispackaged in bags.

The sterilization is usually effected in a sealed sterilization chamberof a sterilizer, into which the medical device is introduced.

In order to avoid endangering patients on whom the medical device is tobe used, it must be ensured that the medical device is actually sterile,i.e. substantially free of germs, after the sterilization process hasbeen carried out.

While the fundamental effectiveness of known sterilization processes hasbeen sufficiently proven scientifically, the actual effectiveness of asterilization process when applied to a particular medical device isdependent on many parameters, including shape and material properties ofthe medical device, and on the selected process parameters of thesterilization process, e.g. the temperature profile, quantities of mediaused and the process duration.

As individually checking the sterility of a medical device is impossiblein practice, without in the process at least limiting the availabilityfor use of the medical device, proving the sterility is effected by avalidation of the sterilization process used. Here, it is scientificallyproven that a sterilization process carried out with particularparameters always achieves the desired result. Here, the desired resultis defined via the factor by which a germ load in the medical device isreduced by the sterilization process. An effective sterilization can beregarded as having been effected e.g. when the germ load has beenreduced by a factor of 10¹².

A current process for determining the effectiveness of a sterilizationprocess consists of introducing a sample which is provided with a knowngerm load at a critical point of a medical device. A critical point heredenotes a point of the medical device at which a particularly smalleffect of the sterilization process is expected, for example because thepoint heats up particularly slowly, or because it is particularlydifficult for media used for the sterilization to reach.

The medical device is then subjected to the sterilization process. Thesample is then removed and the remaining germ load is determined.

Paper strips, which are inoculated with particularly temperature-stablegerms, for example with Geobacillus stearothermophilus, are often usedas samples.

If the evaluation of the sample reveals that the necessary reduction ofthe germ load has been achieved, the sterilization process is regardedas reliable and is validated.

While the described method is widely recognized, it does to some extenthave substantial disadvantages. Firstly, the evaluation of the samplesrequires a substantial outlay on equipment and time, as an incubation ina culture medium lasting several days is required first before anevaluation of the remaining germs, in order to arrive again at a germdensity to be evaluated meaningfully. Secondly, the introduction of thesamples into the medical device to be sterilized is often difficult. If,for example, the medical device has a sealed volume, this may have to beopened in order to introduce the sample. The results of the validationcan also be distorted thereby. In addition, it can happen that acritical point of the medical device is difficult for the sample toreach or cannot be reached by it at all, for example if the medicaldevice comprises thin channels or tubes. A further disruptive effectconsists of a sample influencing the concentration of a medium used inthe sterilization process, for example in that a paper strip absorbswater and thus reduces the humidity in its surroundings.

From the patent applications WO 00/27228 A1 and WO 00/27229 A1 processesare known for computationally determining the reduction of a germ loadachieved at a critical point of a food product during a thermalsterilization. For this, however, only the temperature profile at aso-called “Cold Spot” of the product is simulated, the dependence onother media is not taken into account.

In particular in the case of sterilization processes in which more thanone medium is used, these processes are inadequate.

An object of the invention is thus to provide a process for determiningthe effectiveness of a sterilization process for a medical device in asterilizer which is improved with respect to the described problems.

A further object of the invention is to provide an improved process forvalidating a sterilization process for medical devices.

One or more of the named objects are achieved according to a firstaspect of the invention by a process for determining the effectivenessof a sterilization process for a medical device in a sterilizer, withthe steps of: providing a data structure, wherein the data structurerepresents a grid formed of a plurality of three-dimensional cells,recreating the medical device arranged in the sterilizer in the datastructure in such a way that a first plurality of cells of the gridrepresent a body of the medical device and that a second plurality ofcells represent an interior of the sterilizer which is not occupied bythe body of the medical device, recreating an initial state in the datastructure in such a way that each cell of the second plurality of cellsis assigned data with respect to the temperature prevailing at thelocation of the cell, the quantity of a first medium located in the areaof the cell and the quantity of a second medium located in the area ofthe cell, recreating, step by step, changes in the temperature, thequantity of the first medium and the quantity of the second mediumoccurring in each cell of the second plurality of cells during thesterilization process, calculating a reduction of a germ load achievedin each cell of the second plurality of cells during the sterilizationprocess taking into account the prevailing temperature, quantity of thefirst medium and quantity of the second medium in the respective cell ineach step.

It has surprisingly been found that with processes known fromcomputational fluid dynamics, in which a continuous space is dividedinto discrete cells in which constant relationships are assumed in eachcase, not only can flows of media be recreated well, but with it acurrent and an accumulated reduction of the germ load can also becalculated with a high degree of precision for each location of themedical device, even if there is a complex geometry.

In the case of the recreation of sterilization processes with more thanone medium, the quantity of the individual media in each cell of thedata structure is important for several reasons.

Firstly, the individual media can have a substantial influence on theheat transfer between the individual cells, e.g. on the heat transferbetween the interior of the sterilizer and the body of the medicaldevice. Interior of the sterilizer here denotes the total free interiorwhich is not filled by solid constituents of the medical device.Therefore, this also includes internal cavities of the medical device.

Secondly, the quantity of the individual media can also have a directinfluence on the reduction of the germ load.

In general, the temporal progression of the germ load N at one point ofthe medical device can be described with the following differentialequation:

$\frac{dN}{dt} = {{- k}*N}$

Here, k is the so-called deactivation rate, which indicates whatproportion of the germ population is deactivated or killed in aninfinitesimally short time interval dt. Firstly, the deactivation rateis strongly dependent on the temperature, wherein the deactivation raterises approximately exponentially with the temperature. Secondly, thedeactivation rate is also dependent on the heat transfer from the mediumsurrounding a germ to the germ itself. For example, at the sametemperature a much higher deactivation rate can thus result if there isa high proportion of water vapour in the atmosphere than if the air isdry. Of course, the quantity or concentration of directly active mediasuch as ethylene oxide also has a direct influence on the deactivationrate k.

For the computational recreation, the above-named differential equationis replaced by a finite difference equation which, with discrete timeintervals Δt, calculates:

$\frac{\Delta\; N}{\Delta\; t} = {{- k}*N}$

In the case of the above-specified finite difference equation, changesin the germ load due to flow and diffusion are disregarded; these do notplay an appreciable role in usual sterilization processes.

Now, in the process according to the invention, it is calculated in manyindividual steps how the temperature and the quantity of the individualmedia change in the cell of the grid. Causes for the change in thequantities of media are, for example, flow and diffusion processes, butalso heat transfer processes such as for example condensation andevaporation. In each step the resultant change in the germ load is thendetermined for each cell of the grid, with the result that after therecreation of the complete sterilization process the ultimately achievedreduction of the germ load is known for each cell of the grid. Therecreation also relates to the edges of the cells and thus optionallythe surface of the medical device. The total sterilization process isthus computationally recreated or simulated.

The process according to the invention offers the advantage that theeffectiveness of a sterilization process for a particular medical devicecan be determined without this process having to be actually carriedout, and without samples then having to be evaluated in a laboriousmanner. It thereby becomes possible to determine the effects of changeson the effectiveness of the process. Here, both design changes of themedical device and parameter changes of the sterilization process can besimulated. In this way both the medical device and the sterilizationprocess can be optimized with respect to the use of material and energy.

Furthermore the process according to the invention offers the advantagethat points of a medical device which are not accessible to samples canalso be taken into account in the determination of the effectiveness ofa sterilization process.

In a development of a process according to the invention the quantity ofa third medium can additionally be taken into account in each cell.

For example, ethylene oxide or hydrogen peroxide, which are used in gasor plasma sterilization, can be taken into account as the third medium.The quantity of these media in each cell has a direct influence on therespective deactivation rate.

According to a particular development, a phase transition of the first,second and/or third medium can be taken into account in the recreationof the sterilization process.

Thus, for example, a medical device can be provided with a water loadbefore the sterilization in the autoclave, in order to providesufficient water vapour for the actual sterilization procedure. Forthis, a medical device or a gas-filled component of the medical devicecan be exposed to a vacuum first in a pre-treatment, with the resultthat air is sucked out of the medical device, and then an “aeration”with water vapour can be effected. The water vapour then penetrates intothe medical device and in a large part condenses to water droplets onthe surface of the medical device.

These water droplets have to be evaporated first in the actualsterilization process, which has a great influence on the temperatureand media distribution during the sterilization process. By taking thisphase transition into account, the recreation of the process becomeseven more precise.

According to a further design of a process according to the invention ashape change of the medical device can additionally be taken intoaccount in the recreation of the sterilization process. For this, thecells of the grid which represent the medical device can be assignedvalues for the elastic and/or plastic behaviour of the respectivematerial.

If now, for example, a water reserve evaporates during the sterilizationprocess in an interior of a flexible medical device, such as a blood,serum or dialysis bag, then the medical device can swell, whereby theflow and diffusion processes are substantially influenced. Taking thisdeformation into account results in an even more precise recreation ofthe sterilization process.

In an additional development of a process according to the invention adiffusion of the first, second and/or third medium through the materialof the medical device can be taken into account in the recreation of thesterilization process.

A diffusion of media can be intentional or even necessary. Thus, forexample, in the case of ethylene oxide sterilization of packaged medicaldevices the ethylene oxide must diffuse through the packaging in orderto reach the actual medical device. Within the meaning of the inventionthe packaging here is to be understood as a constituent of the medicaldevice. However, an unintentional diffusion can also have an appreciableinfluence on the effectiveness of the sterilization process. On thewhole, the validity of the recreation can be increased even further bytaking the diffusion into account.

As a rule air is to be taken into account as the first medium. Water,which can be present both as a liquid and as water vapour, is usually tobe taken into account as the second medium. Ethylene oxide or hydrogenperoxide comes into consideration as the third medium or, in the absenceof water, as the second medium.

One or more of the above-named objects are achieved according to asecond aspect of the invention by a process for validating asterilization process for medical devices, with the steps of: defining areduction of a germ load to be achieved by the sterilization process;carrying out a process according to the first aspect of the invention;comparing the reduction of the germ load determined in each cell of thesecond plurality of cells; and grading the sterilization process aseffective if the necessary reduction of the germ load has been achievedfor each of the cells, or grading the sterilization process as noteffective if the necessary reduction of the germ load has not beenachieved for at least one of the cells.

The described process greatly simplifies the validation of asterilization process as the introduction of samples and the subsequentevaluation of the samples can be dispensed with. As the validation of asterilization process for a particular medical device is a prerequisitein many legal systems for the approval both of the sterilization processand of the medical device itself, the approval of new medical devicescan be simplified and accelerated, with the result that new andinnovative medical devices can be put on the market, and thus benefitpatients, more quickly.

In a further development of the process according to the invention forvalidating a sterilization process, a checking process can additionallybe carried out, with the steps of: introducing a sample provided with aknown germ load at a predefined point of a medical device to besterilized, carrying out the sterilization process to be validated onthe medical device, determining the reduction of the germ load of thesample achieved by the sterilization process, and grading thesterilization process as effective only when the reduction of the germload of the sample actually achieved corresponds sufficiently preciselyto the reduction of the germ load calculated for the correspondingpoint.

Even though the positioning and subsequent evaluation of a sample isnecessary for the validation according to the described furtherdevelopment, the process is advantageous compared with the validationaccording to the state of the art. Thus, for example, it can be provedby the simulation that the location at which the sample was introducedis actually a critical location of the medical device, thus a locationat which the sterilization process brings about the smallest reductionof the germ load. Even if the critical location of the medical devicecannot be reached by a sample, it can be proved with the describedprocess that the result of the simulation at the location at which thesample was introduced matches the actual result of the sterilizationprocess. It can then be assumed that the simulation result is alsocorrect for the actually critical location.

One or more of the named objects are achieved according to a thirdaspect of the invention by a data processing system, comprising at leastone processor, a memory, input means and output means, and which isdeveloped in that program code information which, when executed by theprocessor, is able to prompt the latter to execute a process accordingto the above descriptions is stored in the memory.

The data processing system can comprise a computer customary in thetrade, which is expediently equipped for the CPU-intensive process withone or more powerful processors and enough RAM.

The input means can, in addition to usual input means such as keyboard,mouse, touchscreen etc., also comprise an interface with a network, viawhich the data processing system is connected to a database in whichinformation about geometric and material-typical properties of one ormore medical devices is stored.

The output means can, in addition to usual output means such as monitorand/or printer, also comprise a storage medium, on which the results ofthe described processes are stored as data. These data can comprisetables, in which the results are represented numerically. The data canalso comprise images and/or videos, by which the progression or theresult of the described processes is visualized.

The program code information can be stored in the form of an executablecomputer program on a storage medium of the computer, for example on ahard drive.

One or more of the named objects are achieved according to a fourthaspect of the invention by a computer program product, comprising a datacarrier and program code information stored on the data carrier which,when executed by a processor, is able to prompt the latter to execute aprocess such as described previously.

One or more of the named objects are achieved according to a fifthaspect of the invention by a sterilized medical device, which has beensubjected to a sterilization process, the effectivity of which has beendetermined by a method as described above, or which has been validatedby a method as described above.

One or more of the named objects are achieved according to a sixthaspect of the invention by a medical device, which has been produced ina sterilizer, wherein the effectivity of a sterilizing method used inthe sterilizer has been determined by a method as described above, orwhich has been validated by a method as described above.

The sterilizer encompasses all means required for executing therespective sterilizing method. By example, the sterilizer shallencompass means required for aeration with water vapour, and also anautoclave chamber.

The invention is explained in more detail below with the aid of someexemplary representations. The embodiment examples represented are toserve merely for the better understanding of the invention, withoutlimiting it.

There are shown in:

FIG. 1: a medical device,

FIG. 2: a sterilizer for a medical device,

FIG. 3a : a sectional representation of the medical device according toFIG. 1,

FIG. 3b : a section of FIG. 3a with a grid structure,

FIGS. 4a-4c : possible visualizations of a simulation result,

FIG. 5: a data processing system.

FIG. 1 shows a medical device, in the example represented it is a bagset 1 for peritoneal dialysis.

In peritoneal dialysis a dialysis fluid is introduced into the patient'sabdominal cavity via a catheter in the abdominal wall. Via the extensivecontact of the dialysis fluid with the peritoneum, which surrounds allthe organs located in the abdominal cavity, harmful substances areflushed out of the patient's blood into the dialysis fluid, and thusremoved from the blood. After a certain residence time, which is as arule approximately four hours, the dialysis fluid loaded with harmfulsubstances, the so-called dialysate, is drained off from the patient'sabdomen and replaced by fresh dialysis fluid.

The bag set 1 comprises a solution bag 2, which has two chambers 3, 4filled with dialysis fluid, as well as a technically required emptychamber 5. The empty chamber 5 is also called the lambda chamber becauseof its shape. Each of the chambers 3, 4, 5 is provided with a connectingpiece. Two components of a dialysis solution, a glucose solution and abuffer solution for regulating the pH of the final dialysis solution arestored in the chambers 3, 4. The glucose solution and the buffersolution are not mixed until they are used, thus not until immediatelybefore introduction into the patient's abdominal cavity.

Furthermore, the bag set 1 comprises an empty drainage bag 10, which isprovided with two connecting pieces. The drainage bag 10 has a singlereceiving chamber 11, not visible in FIG. 1, for dialysate. In order tomake it easier to run the dialysate into the drainage bag 10, the lattercan be equipped with stiffening rods, not represented.

A central connector 15 of the bag set 1 serves to connect the bag set tothe patient's catheter. The central connector 15 is connected to thesolution bag 2 and to the drainage bag 10 via tubes 16, 17. Either thesolution bag 2 or the drainage bag 10 can be connected to the cathetervia a valve, not represented.

The tube 16 connects the central connector 15 to the solution bag 2. Inthe packaged state, the tube 16 is rolled up spirally, it is thereforealso called a solution coil. At this stage the tube 16 is connected tothe connecting piece of the solution bag 2, which opens into the emptychamber 5.

Not until immediately before the use of the bag set 1 is the tube 16connected to the chambers 3 and 4 previously separated from each other,in order to guide the now mixed solutions to the central connector 15.

The tube 17 connects the central connector 15 to one of the connectingpieces of the drainage bag 10. A second connecting piece can be providedfor example in order to gain access to the drainage bag with the aid ofa syringe. Then, for example, a test for analysis of the dialysate canbe performed. The tube 17 is likewise rolled up in the packaged stateand is called a drainage coil.

The individual components of the bag set 1 are subjected to apre-treatment before being assembled, in order to deposit water in allair-filled spaces for the later sterilization procedure.

For this, the components are positioned in a vacuum chamber. Thischamber is then evacuated to a pressure of for example between 150 hpaand 300 hpa residual pressure and then, for example with the aid of asteam nozzle, flooded abruptly with water vapour, for example to apressure of approximately 1450 hpa. In the process the vapour penetratesinto the cavities of the components of the medical device and condensesto water droplets. This pre-treatment is called steaming.

The bag set 1 is then assembled and shrink-wrapped in a plastic bag, notrepresented, for storage and for transport.

The finally packaged bag set 1 must be sterilized before use, in orderto avoid an infection of the patient. For this, as a rule several bagsets are introduced into a sterilizer, which is represented in FIG. 2.

FIG. 2 shows a sterilizer for medical devices which is an autoclave 20.The autoclave has a sterilization chamber 21, in which in the examplerepresented 24 packaged bag sets 1 are arranged on suitable mesh racks.The sterilization chamber 21 can be closed in a pressure-resistantmanner by a door, not represented.

During the sterilization process the sterilization chamber 21 is exposedto superheated steam at high pressure. For example a pressure of 2600hpa and a temperature of approximately 130° C. can be achieved here.

Due to the combination of high pressure and high temperature germspresent in the bag system 1 are killed, with the result that they can nolonger cause an infection of the patient.

The effectiveness of the sterilization process depends on variousparameters. In addition to the pressure and temperature in thesterilization chamber 21 and the treatment duration, these also includethe temperatures actually achieved in the medical device as well as thequantities of water available in the cavities, their evaporation rateand the resultant water vapour concentrations.

According to a conventional method for determining the effectiveness ofa sterilization process for medical devices one or more models of themedical device to be sterilized are provided with samples which have aknown loading with test germs. As a rule particularly temperature-stablegerms are used as test germs, for example of the species Geobacillusstearothermophilus.

The models equipped in this way are then subjected to the sterilizationprocess in question, and then the effect of the sterilization process onthe samples is determined. For this, they are incubated in a culturemedium over several days and the population of the test germs isevaluated.

In order to reduce the outlay associated with the conventional method, amethod is proposed here for determining the effectiveness of thesterilization process by means of a simulation. For this, the medicaldevice and the interior of the sterilizer are recreated in athree-dimensional grid. This is represented schematically in FIGS. 3aand 3 b.

FIG. 3a shows a section through the bag set 1 along a plane which runsthrough the line A-A′ (FIG. 1) and runs perpendicular to the plane ofextension of the bags 2, 10. It is recognizable that the solution bag 2is formed of a lower film ply 30 and an upper film ply 31, which areconnected along connection lines 32, 33, 34, 35 such that the chambers3, 4 for the dialysis solutions and the lambda chamber 5 form.

The drainage bag 10 likewise consists of a lower film ply 40 and anupper film ply 41, which are connected along connection lines 42, 43such that the receiving chamber 11 forms.

At the connection lines 32, 33, 34, 35, 42, 43 the respective film plies30, 31, 40, 41 can be glued, heat-sealed, or otherwise connected to eachother such that a substantially gas- and liquid-tight connectionresults.

In FIG. 3b an enlargement of a section X from FIG. 3a is represented,which represents the lower film ply 30 and the upper film ply 31 of thesolution bag 2 in the area of the lambda chamber 5. In addition, athree-dimensional grid 100 is represented here, which serves to recreatethe bag set 1 in a data structure.

Although the grid 100 in FIG. 3b is represented two-dimensionally forthe sake of clarity, it is actually a three-dimensional grid consistingof a plurality of grid cells Z. In the example represented all the cellsZ of the grid are the same size and shape, for example tetrahedrons.Depending on the complexity of the shape of the medical device,individual ones of the cells can also have a different shape and/orsize.

For each of the cells Z it is defined whether there is a physicalconstituent of the medical device, such as the film plies 30, 31 of thesolution bag 2 at the locations of the cells Z₁, Z₂, at thecorresponding point, or whether it is a cell in a cavity or in thesurroundings of the medical device, such as the cells Z₃, Z₄.

For each cell Z of the grid 100 a dataset is provided in the datastructure.

For the cells which are filled by physical constituents of the medicaldevice, the dataset contains the prevailing temperature as well asmaterial data of the medical device, such as the elastic properties ofthe material, the heat capacity, the thermal conductivity, as well asthe permeability for different media (air, water, steam, etc.). For theother cells, the dataset contains the quantities of the media present inthe respective cell (air, water, water vapour, etc.) as well as dataabout their thermodynamic state (temperature, pressure, flow rate anddirection, etc.). Additionally, for each cell representing a cavity anitem of information with respect to a germ load or an achieved reductionof the germ load is provided.

Boundary surfaces G, which are recognizable as lines in FIG. 3b , areformed between neighbouring cells Z.

The data structure is then filled with data, so that it represents aninitial state at the start of the sterilization process. For example,approximately room temperature will be present in all the cells, and thepressure is approximately 1000 hpa in each cell which represents acavity.

At the same time, a mixture of air and water vapour, for example steamor steam-air mixture with approx. 2.6 to 3.6 bar absolute pressure and atemperature of for example 130° C., will be present in all the cellswhich are located outside the medical device.

In the case of cells which are located in sealed cavities of the medicaldevice, other relationships can result due to the previous steaming.Thus, some cells here are optionally filled with water, while in othercells there is a mixture of air and water vapour and also condensedwater, which corresponds to a complete saturation.

For cells in cavities of the medical device filled with fluid, all thecells are correspondingly filled with the respective fluid.

Subsequently it is computationally determined step by step how therelationships in the individual cells Z of the grid change while thesterilization process is being carried out. A time interval recreated bya computation step can be, for example, one second, but longer orshorter time intervals can also be realized.

During a heating phase of the sterilization process the sterilizationchamber 21 is supplied with superheated steam, with the result that insome cells, which represent this space, pressure, water vapour quantityand temperature rise. As soon as there are differences between twoneighbouring cells, a transfer of energy and/or media through therespective boundary surface between the cells results. The herebyresultant changes of state of the individual cells are determinedcomputationally. The computation methods to be used for this aresufficiently known from computational fluid dynamics and therefore neednot be explained in more detail here. The following effects aresubstantially to be taken into account here:

Temperature equalization: if there is a temperature difference betweentwo neighbouring cells, heat energy is transferred through the boundarysurface from the warmer to the colder cell, whereby the temperaturesequalize.

Pressure equalization: if there is a pressure difference between twoneighbouring cells, some of the media will flow out of the cell withhigher pressure through the boundary surface into the cell with lowerpressure, with the result that the pressures equalize.

Concentration equalization: if there is a difference in theconcentration of a medium between two neighbouring cells, or adifference in the partial pressures of the media, some of the mediumwill diffuse through the boundary surface into the cell with lowerconcentration or partial pressure, with the result that theconcentrations or partial pressures equalize.

Gravity: if there is a height difference between two cells, some of themedia will flow out of the higher cell through the boundary surface intothe lower cell.

Natural convection: if there is a difference in density between twoneighbouring cells, this results in a natural convection.

The interaction of pressure equalization, gravity, convection andconcentration equalization (diffusion) leads to a height-dependentchange in the mixing ratio of gaseous media such as air, water vapourand ethylene oxide. This can have effects on the effectiveness of thesterilization process and therefore has to be recreated computationallyas precisely as possible.

After completion of the heating phase the state of the atmosphere in thesterilization chamber 21 is kept constant, with the result thatessentially only equalization procedures take place within the medicaldevice. The progression of these equalization procedures is, however, ofgreat importance to the success of the sterilization process, thereforethe total duration of the sterilization process is further recreated orsimulated according to the above-described method.

A cooling process, in which above all the dialysis solutions present inthe solution bag are to be cooled in order to prevent prematuredegradation, downstream of the sterilization process can on the otherhand optionally be excluded.

Further media can be taken into account in the simulation. Thus, forexample, a biocidal gas such as ethylene oxide can be introduced intothe sterilization chamber and diffuse into the medical device. Thecorresponding diffusion procedures can be recreated by the simulationprocess. For example, the injection of ethanol for example into plug-inconnections can thus also be readjusted.

The diffusion of media through the material of the medical device can bemodelled in the simulation by adding to the data structure data on theabsorbency (for example as permeability or diffusion data) of thematerial for individual media. If, for example, the material can absorba certain quantity of water vapour, water vapour will diffuse via aboundary surface into the respective cell if the concentration of thewater vapour in the neighbouring cell is high enough. Thus, water vapourcan disperse in the material slowly cell by cell and even escape againat boundary surfaces to cavities where there is a lower concentration.Thus, for example, water vapour can diffuse from the sterilizationchamber through the film plies 30, 31 into the lambda chamber 5. In thesame way, the diffusion of other media such as ethylene oxide or ethanolcan also be simulated.

During the sterilization process further effects can emerge, which haveto be taken into account in the simulation. Thus, for example, in sealedvolumes of a medical device an increase in the internal pressure willresult. This rise in pressure is particularly relevant when liquidwater, which evaporates due to the temperature increase, is present inthe corresponding volumes at the start of the sterilization process. Theevaporation procedure must be taken into account in the simulation as ithas a substantial influence on the heat distribution in the medicaldevice. Likewise, at some points of the medical device condensation canoccur, which likewise influences the temperature distribution.

Due to the evaporation of water the lambda chamber 5 or the receivingchamber 11 can furthermore swell, whereby the geometry of thecorresponding volumes changes.

Allowances can be made for this effect in different ways. Firstly, theelastic and/or plastic deformability of the material of the medicaldevice can be stored in the data structure. In each computation step itcan then be determined whether a force is acting on a cell whichrepresents a physical constituent of the medical device, with the resultthat it moves. If a movement of the material in the cell is established,either the grid can remain unchanged and the movement can be imaged inthat the corresponding state data are assigned to a neighbouring cellinto which the material has moved. It can also become necessary forindividual cells to have to be added or removed. However, this can havethe result that after the shift cells exist which are no longer assignedany state data, which leads to problems.

A better solution is to construct the entire grid dynamically such thatthe size and position of the individual grid cells can change, in orderto allow for such expansion effects. Here, it is to be borne in mindthat in areas in which a clear volume change is to be expected asufficiently fine grid structure is chosen in order that the result doesnot become imprecise due to grid cells ultimately being too large.

As a decisive part of the simulation, in each computation step for eachcell of the grid which does not correspond to a physical constituent ofthe medical device the effect of the respectively prevailing state on apossible germ population is calculated. During the definition of theinitial state each cell can be assigned a particular germ load, forexample an occupancy with 10⁶ germs of the species Geobacillusstearothermophilus.

With the aid of the finite difference equation ΔN_(i)=−k_(i)*N_(i)*Δtthe alteration of the germ load and the remaining germ load are thendetermined. In the process the deactivation rate k is determineddepending on the respectively present ambient parameters, thus forexample the temperature, the water vapour concentration and/or theconcentration of active media such as ethylene oxide.

Instead of calculating a notional germ load, in each computation stepand for each computation cell a logarithmic germ reduction F can also bedetermined and then added up in order to determine the germ reductionachieved during the total sterilization process:

$F_{i} = {{\log\frac{N_{i + 1}}{N_{1}}} = {\log( {1 - {k_{i}*\Delta\; t}} )}}$$F_{tot} = {{\log\frac{N_{end}}{N_{start}}} = {\Sigma\; F_{i}}}$

The results of the simulation can be represented or visualized indifferent ways. One possibility is to output the smallest germ reductionachieved in the medical device as a number.

The progression of a parameter of interest over the duration of thesterilization process can be output as a graph for a selected cell.

Further possibilities are to represent selected parameters colour-codedor greyscale-coded in sectional representations of the medical device.Here the state at a particular point in time during the sterilizationprocess can be represented, for example the temperature or the achievedgerm reduction after 1000 seconds, after 2000 seconds and at the end ofthe sterilization process.

In FIGS. 4a to 4c , for example, visualizations of the temperature ofthe dialysis solutions after a sterilization process are represented.FIG. 4a shows the temperature at the outer surfaces of the solutionchambers 3, 4; FIG. 4b shows the temperature in a section parallel tothe surface of extension of the solution bag 2; and FIG. 4c shows thetemperature in a section perpendicular thereto. It is recognizable thatin the example represented a very homogeneous final temperature of thesolutions has been achieved.

The progression of the respective parameters over the duration of thesterilization process can also be provided as a video. In similarrepresentations, pressure, water vapour concentration and/or achievedgerm reduction can also be represented.

The described simulation process can be used to determine theeffectiveness of a sterilization process for a particular medicaldevice, such as for the bag set 1 in the example represented. In thisway, e.g. after a design change or redevelopment of a medical device, itcan be checked whether a known sterilization process is sufficient tosterilize the medical device reliably. In this way the effects ofadjustments on the sterilizability can be tested without the need tomanufacture and sterilize sample copies for every adjustment.

Thereby, new or modified medical devices can be made available to themarket fast, as the effectivity of a suitable sterilization method canquickly be shown.

Parameter changes in sterilization processes can likewise be tested withthe described simulation process for their effects on the result,without having to accept the described outlay for performance andsampling.

In order to test individual components of a medical device with respectto their sterilizability, it can make sense to limit the simulationinitially to these components and their immediate surroundings. Thenecessary computational outlay can thereby be reduced substantially.However, a complete simulation should always be effected for aconclusive assessment.

Finally, it is even conceivable to use the results of the describedsimulation process to validate a sterilization process for the legalapproval of a new or altered medical device or a sterilization process.

For this, a germ reduction to be achieved by the sterilization processis predefined, which is for example a 12-log reduction, thus a germreduction by a factor of 10¹². It is then checked, with the aid of thesimulation, that the required germ reduction is achieved at every pointof the medical device. If the required reduction is achieved, thesuccessful sterilization is validated and the medical device can beapproved.

The reliability of the proof can be further increased if a sampling witha sample is effected in addition to the simulation and the result of thesimulation is compared with the result of the sampling. The approval canthen be made dependent on the results matching.

Here, in contrast to the conventional validation process, the samplingcan be effected at a point of the medical device which is not a criticalpoint, as only the match with the simulation result needs to be proved.The outlay on the sampling can hereby be reduced. Influences of thesample on the media distribution in the medical device can be taken intoaccount in the simulation or compensated for by a corresponding additionor deduction of media.

In contrast to the conventional validation process, proving the matchbetween simulation and sampling can optionally be effected in aninterrupted sterilization process, for example when the actuallynecessary germ reduction has not yet been achieved. This has theadvantage that a larger population of test germs, which can be evaluatedmore easily, is still present on the sample after the sterilizationprocess.

By the validation process described above, a new or modified medicaldevice can be made available to the market even faster.

In the described simulation process it must be taken into account thatthe initial state is possibly not identical for every individual medicaldevice. Thus, in particular, the position and/or size of water dropletswhich enter the medical device due to the steaming can be random and candiffer from medical device to medical device. Precisely in the case ofmedical devices with awkward geometries, for example long tube sections,the position of water droplets in the tube section can have relevanteffects on the result of the sterilization process.

It can therefore be necessary to model some possible distributions ofthe water droplets and to simulate the effects separately. For avalidation, the distribution would then have to be based on which onebrings the poorest sterilization result.

In order to determine the effect of the steaming of the medical deviceand a resultant distribution of water droplets in the medical device, asimulation process designed analogously to the above-describedsimulation process of the sterilization process can likewise be carriedout for the steaming process. However, it must be taken into accounthere on the one hand that the actual position and size are randomlyaffected strongly by water droplets forming due to condensation, withthe result that at best estimates are possible. On the other hand thewater droplets can move and merge in the medical device, if the medicaldevice is moved between the steaming and the sterilization.

The described simulation process can be carried out on a data processingsystem, such as is represented in FIG. 5.

The data processing system 100 comprises a central processing unit 101with at least one processor 102 and a storage element 103. The at leastone processor 102 can be a powerful multi-core processor which isoptimized for the execution of complex mathematical tasks. The storageelement 103 can comprise writable components (RAM) and non-writablecomponents (ROM). The storage element 103 preferably has a large storagecapacity and a high write and read speed.

The central processing unit 101 can be formed by a computer customary inthe trade, e.g. a PC.

The central processing unit is connected to input means and outputmeans, via which information about the sterilization process to besimulated can be input and output. The input means can comprise e.g. akeyboard 104 and a mouse 105. The output means can comprise a monitor106. If the monitor 106 is a touchscreen, it can at the same time alsofunction as input means.

The central processing unit can be connected to a database 111, in whichdesign data for one or more medical devices, one or more sterilizersand/or data for one or more sterilization processes are stored, directlyor via a network 110. The processor 102 can access the data stored inthe database 111 in order to recreate a medical device and/or asterilizer in a data structure, and/or in order to recreate asterilization process by means of the above-described simulationprocess.

The central processing unit 101 is furthermore connected to a write/readdevice 112 for the data carrier 113. In the example represented the datacarrier 113 is a CD or DVD, alternatively other known removable ornon-removable data carriers can be used.

Program code information, which can be transferred into the storageelement 103 by the processor 102, can be stored on the data carrier 113.From the storage element 103 the processor 102 can then read and executethis program code information in steps, whereby the processor isprompted to execute the above-described simulation process.

The central processing unit can likewise use the write/read device tostore results of the simulation process on a data carrier 113.Alternatively, the results can be visualized on the monitor 106 and/orstored in the database 111.

The representation of the data processing system 100 in FIG. 5 isgreatly simplified for a better overview. In particular, the at leastone processor 102 in a real data processing system is not connected tothe peripheral devices 104, 105, 106, 112 directly, but via suitableinterface elements.

1. A process for determining the effectiveness of a sterilizationprocess for a medical device in a sterilizer, with the steps ofproviding a data structure, wherein the data structure represents a gridformed of a plurality of three-dimensional cells, recreating the medicaldevice arranged in the sterilizer in the data structure in such a waythat a first plurality of cells of the grid represent a body of themedical device and that a second plurality of cells represent aninterior of the sterilizer which is not occupied by the body of themedical device, recreating an initial state in the data structure insuch a way that each cell of the second plurality of cells is assigneddata with respect to the temperature prevailing at the location of thecell, the quantity of a first medium located in the area of the cell andthe quantity of a second medium located in the area of the cell,recreating, step by step, changes in the temperature, the quantity ofthe first medium and the quantity of the second medium occurring in eachcell of the second plurality of cells during the sterilization process,calculating a reduction of a germ load achieved in each cell of thesecond plurality of cells during the sterilization process taking intoaccount the prevailing temperature, quantity of the first medium andquantity of the second medium in the respective cell in each step. 2.The process according to claim 1, wherein a quantity of a third mediumpresent in each cell (Z) of the second plurality of cells isadditionally taken into account.
 3. The process according to claim 1,wherein a phase transition of the first, second and/or third medium istaken into account for the recreation of the sterilization process. 4.The process according to claim 1, wherein a shape change of the medicaldevice is taken into account for the recreation of the sterilizationprocess.
 5. The process according to claim 1, wherein a diffusion of thefirst, second and/or third medium through the material of the medicaldevice is taken into account for the recreation of the sterilizationprocess.
 6. The process according to claim 1, wherein the first mediumis air.
 7. The process according to claim 1, wherein the second mediumis water.
 8. The process according to claim 1, wherein the second or thethird medium is ethylene oxide.
 9. A process for validating asterilization process for a medical device, with the steps of: defininga reduction of a germ load to be achieved by the sterilization process;carrying out the process according to claim 1, comparing the reductionof the germ load determined in each cell of the second plurality ofcells; and grading the sterilization process as effective if thenecessary reduction of the germ load has been achieved for each of thecells, or grading the sterilization process as not effective if thenecessary reduction of the germ load has not been achieved for at leastone of the cells.
 10. The process according to claim 9, wherein achecking process is additionally carried out, with the steps of:introducing a sample provided with a known germ load at a predefinedpoint of a medical device to be sterilized, carrying out thesterilization process to be validated on the medical device, determiningthe reduction of the germ load of the sample achieved by thesterilization process, and grading the sterilization process aseffective only when the reduction of the germ load of the sampleactually achieved corresponds sufficiently precisely to the reduction ofthe germ load calculated for the corresponding point.
 11. A dataprocessing system, comprising at least one processor, a memory, inputmeans and output means, wherein program code information which, whenexecuted by the processor, is able to prompt the latter to execute theprocess according to claim 1 is stored in the memory.
 12. A computerprogram product, comprising a data carrier and program code informationstored on the data carrier which, when executed by a processor, is ableto prompt the latter to execute the process according to claim
 1. 13. Asterilized medical device, wherein the medical device has been subjectedto a sterilization process, the effectivity of which has been determinedby the process of claim
 1. 14. A sterilized medical device, wherein themedical device has been subjected to a sterilization process, which hasbeen validated by the process of claim
 9. 15. A sterilized medicaldevice, wherein the medical device has been produced in a sterilizer,wherein the effectivity of a sterilization method used in the sterilizerhas been determined in the process of claim
 1. 16. A sterilized medicaldevice, wherein the medical device has been produced in a sterilizer,wherein the effectivity of a sterilization method used in the sterilizerhas been validated by the process of claim 9.